Inflammation is the body's defense mechanism in response to endogenous or exogenous assault on the human body. Physical, chemical or infectious causes can be the source of exogenous agents of inflammation. Metabolic causes, vascularization problems, or an abnormal immune response can be the source of endogenous agents of inflammation. In the presence of one of these agents, the inflammation mechanism will respond by a series of successive steps:                vascular exudative reaction causing congestion (hyperaemia), an inflammatory edema and a leukocyte diapedesis,        cellular reaction consisting of the formation of inflammatory granuloma,        debridement, and        repair and healing of the injured area.        
However, inflammation can sometimes be detrimental, due to the persistence of a pathogen or endogenous agent, such as autoimmunity in rheumatoid arthritis. The damage to the body will then continue to develop leading to an uncontrolled immune response and a chronic inflammation accompanied by tissue destruction such as joint tissue.
Rheumatoid arthritis is an autoimmune, progressive, chronic, inflammatory rheumatic disease that affects joints symmetrically and which results in pain, swelling and stiffness of joints when waking up. It is called progressive because, in most cases, it progresses by inflammatory spurts interspersed with more or less long periods of calm.
It can also occur in other tissues and these extra-articular manifestations may then endanger the patient's life.
Rheumatoid arthritis affects about 1% of the population with predominance in women, 3 cases for 1 in men, knowing that the incidence increases with age.
The first symptoms appear in the small joints of the fingers or feet. Over time, chronic inflammation leads to the destruction of bone and cartilage and a progressive disability. If the inflammation persists, it can destroy cartilage, the surrounding bone tissue, the tendons and the periarticular ligaments. Thus, the disease often leads to joint deformity and disability. Rheumatoid arthritis is more particularly characterized by inflammation of the synovial membrane of the joints leading to abnormal infiltration of inflammatory cells in the synovial fluid.
Initially, there is an abnormal proliferation of blood vessels which allows influx of pro-inflammatory cells (lymphocytes including CD4, monocytes, polymorphonuclear leukocytes, neutrophils) in the synovium and the intra-articular space.
The hyperplasia of synovial fibroblasts and the infiltration of lymphocytes (T, CD4 and B) and macrophages then lead to the formation of a synovial pannus, which results in inflammation of the synovial membrane, also called synovitis. These different cells proliferate abnormally, invade the bone and cartilage, produce a large amount of pro-inflammatory cytokines and metalloproteinases, and trigger the formation and activation of osteoclasts. The particularly abundant proinflammatory cytokines are: TNF-α (Tumor Necrosis Factor α), IL-1, IL-6, IL-12 and IL-17, the term IL designating interleukin.
The destruction of the joint is secondary to the erosion of the bone and cartilage degeneration. The erosion is promoted by cytokine RANKL while chondrolysis is promoted by the metalloproteinase enzyme. These two molecules are produced by cells which make up the synovium under the effect of TNF-α and IL-1.
The cells will then try to counter this degradation but osteoclasts, whose role is to manufacture bone, will produce it in an uncontrolled manner thus causing the deformation and ossification of the joints.
The treatment of rheumatoid arthritis should be initiated as soon as possible after the discovery of the disease in order to slow the inflammatory process to prevent joint injuries and deformations.
Traditional treatments consist of administering anti-inflammatory agents to suppress inflammation of the joints and cytokine production. Immunomodulatory medications of the immune system are also used.
The new current therapies are focusing in particular on TNF-α or IL-1 blocking agents, such as Etanercept, Infliximab, Adalimumab and Certolizumab pegol.
The responses to treatment vary among individuals and the stage of the disease. Therefore, the search for alternative treatments is important so as to offer new solutions for patients resistant to existing treatments.
In addition, the treatment of rheumatoid arthritis is quite costly to society due to very expensive anti-inflammatory treatments and the patient's disability that may result. Indeed, treatments for inflammatory diseases are to be taken over the long term to get results, that is to say, to stop the progression of the disease, the inflammatory relapses, and to stabilize and keep the disease in a state of remission.
Similarly, the prolonged use of anti-inflammatory drugs by the patient may cause side effects such as weight gain, gastrointestinal disturbances, and/or increased risk of osteoporosis and hypertension.
As such, probiotics could be an interesting alternative.
The term “probiotic” is used to define living microorganisms which, when incorporated in sufficient quantity, exert a positive effect on health, comfort and well-being, beyond the traditional nutritional effects.
WO2007/133188 discloses the use of an anti-fungal bacterial composition comprising at least one bacterium selected from Bacillus subtilis, Bacillus coagulans, and Enterococcus faecalis, to stimulate an antifungal response and for the treatment of many, very different pathologies, ranging from autism to vaginal infections and endometriosis, and among which rheumatoid arthritis is mentioned. That document does not disclose specific strains of bacteria that can be used in the antifungal composition.
WO2009/026306 discloses such a composition comprising three strains of bacteria, namely Bacillus subtilis, Bacillus coagulans and Enterococcus faecium or faecalis, for the prevention and/or treatment of many, very different pathologies, ranging from autism to vaginal infections and endometriosis, and among which rheumatoid arthritis is mentioned. That document does not disclose specific strains of bacteria that can be used in the composition.
Yet, it is known that the probiotic effect of a given strain, whether it is a yeast strain or a bacterial strain, is specific to this strain, and not of the type or even the species considered. Also, there is still a need to find new therapies for the prevention and/or treatment of chronic inflammatory diseases, alternative to the existing ones, less expensive and with fewer side effects.